Influenza virus is an enveloped virus which contains eight separate segments of negative-stranded RNA genome. There are two spike glycoproteins on the surface of the viral membrane envelope, the receptor binding hemagglutinin (HA), and the neuraminidase (NA). The core ribonucleoprotein (RNP) encapsulated in the viral membrane envelope is composed of an RNA polymerase and RNA-binding nucleoproteins (NP) (1). The interaction of RNPs with the membrane is mediated by the matrix protein M1 (252 amino acids, Mr=27 kd), which are tightly associated with the RNP cores while interacting with the cytoplasmic tails of the spike glycoprotein and the viral membrane (2). Through the binding of hydrophobic domains to the virion lipid envelope, M1 maintains the structural integrity of the virus particle (3,4). On the other hand, the interaction of M1 with RNP cores is mostly electrostatic at neutral pH (5,6). The M1 can easily be dissociated from the RNP cores by low pH treatment (7,8).
In addition to packaging the RNP cores during virion assembly, M1 also directs the transportation of RNPs into or out of the nucleus (9,10). Upon entry of the virus into the new host cell, M1 is dissociated from RNPs as the result of reducing pH in the fusion endosome, allowing the RNPs to enter the nucleus. When progeny viral RNPs are produced, newly synthesized M1 escort the RNPs out of nucleus and target them to the assembly site on the cellular membrane where HA and NA are located. It is therefore highly desirable to provide a method of deducing the crystal structure of M1 and of providing a method of using this structure provide antiviral candidates and M1 inhibitors.